Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2136 West Mall, Vancouver, British Columbia, V6T 1Z4, Canada.
Psychopharmacology (Berl). 2019 Sep;236(9):2699-2712. doi: 10.1007/s00213-019-05244-w. Epub 2019 Apr 10.
Nucleus accumbens (NAc) dopamine (DA) plays an integral role in overcoming effort costs, as blockade of D and D receptors reduces the choice of larger, more-costly rewards. Similarly, the stress neuropeptide corticotropin-releasing factor (CRF) modulates DA transmission and mediates stress-induced alterations in effort-related choice.
The current study explored how excessive stimulation of different DA receptors within the NAc core and shell alters effort-related decision-making and compared these effects to those induced by CRF stimulation.
Male Long Evans rats were well-trained on an effort-discounting task wherein they choose between a low-effort/low-reward and a high-effort/high-reward lever where the effort requirement increased over blocks (2-20 presses). Dopamine D (SKF 81297, 0.2-2 μg), D (quinpirole, 1-10 μg), or D (PD 128,907, 1.5-3 μg) receptor agonists, or CRF (0.5 μg), were infused into the NAc core or shell prior to testing.
Stimulation of D receptors with quinpirole in the NAc core or shell markedly reduced the choice of high-effort option and increase choice latencies, without altering preference for larger vs smaller rewards. Stimulation of D or D receptors did not alter choice, although SKF 81297 infusions into the shell reduced response vigor. In comparison, core infusions of CRF flattened the discounting curve, reducing effortful choice when costs were low and increasing it when costs were high.
Excessive stimulation of NAc D receptors has detrimental effects on effort-related decision-making. Furthermore, CRF stimulation induces dissociable effects on decision-making compared with those induced the effects of stimulation of different DA receptors.
伏隔核(NAc)中的多巴胺(DA)在克服努力成本方面起着至关重要的作用,因为 D 和 D 受体的阻断会减少对更大、成本更高的奖励的选择。同样,应激神经肽促肾上腺皮质释放因子(CRF)调节 DA 传递,并介导应激引起的与努力相关的选择改变。
本研究探讨了 NAc 核心和壳内不同 DA 受体的过度刺激如何改变与努力相关的决策,并将这些效应与 CRF 刺激引起的效应进行了比较。
雄性长爪沙鼠在努力折扣任务中接受了良好的训练,在该任务中,它们在低努力/低回报和高努力/高回报杠杆之间进行选择,其中努力需求随着块的增加而增加(2-20 次按压)。DA D(SKF 81297,0.2-2μg)、D(喹吡罗,1-10μg)或 D(PD 128,907,1.5-3μg)受体激动剂,或 CRF(0.5μg),在测试前被注入 NAc 核心或壳内。
在 NAc 核心或壳内用喹吡罗刺激 D 受体显著减少了高努力选择,并增加了选择潜伏期,而不改变对较大与较小奖励的偏好。刺激 D 或 D 受体不会改变选择,尽管 SKF 81297 注入壳内会降低反应活力。相比之下,CRF 核心内注射会使折扣曲线变平,当成本较低时减少费力的选择,当成本较高时增加选择。
NAc D 受体的过度刺激对与努力相关的决策有不利影响。此外,与刺激不同 DA 受体的效应相比,CRF 刺激对决策产生了可区分的效应。